Hello, A yearly allocation for the LCRC cluster has been requested with the following updated information: Submitter/PI: David Tiede Project Name: protein_e-wire2 Division: CSE Project title: Solar energy conversion in biomimetic molecular architectures Associated funding: This project is supported by three funding programs within the DOE-BES Division of Chemical Sciences, Geosciences, and Biosciences: i) Solar Photochemistry; ii) Photosynthetic Systems; iii) Energy Frontier Research Center: Argonne Northwestern Solar En Other Systems: N/A Science: This computational project will supplement our experimental work on construction and characterization of water-splitting catalysts and biomimetic molecular architectures for solar energy conversion. The first aim is to explore replica-exchange all-atom Molecular Dynamics (MD) simulations as a tool to achieve a better sampling and to predict impact of protein mutations and chemical modifications on conformational dynamics and structural stability with various photosensitizers and photosensitizer-catalyst dyads covalently linked to PpcA, a multi-heme c-type cytochrome from Geobacter sulfurreducens. These results will facilitate interpretation of kinetic electron transfer rates as well as Small- and Wide-Angle X-ray Scattering (SAXS, WAXS) as well as NMR data to provide an insight into strategies for optimization of electron transfer rates within biomimetic hybrids. The second aim is to use replica-exchange MD to simulate equilibrium positions and dynamics of mutation s needed in order to tune redox potentials of PpcA hemes. Our third goal is to use several types of ligand docking simulations to screen and optimize ligand binding sites on PpcA protein surface. Project description: We are developing biomimetic molecular architectures for efficient solar energy conversion using artificial and natural photosensitizers combined with natural and genetically engineered host systems capable to support long-lived charge-separated states and conduct charges away from the photosensitizers. We recently developed and characterized a series of six cysteine mutants of PpcA, a multiheme redox protein from Geobacter sulfurreducens, which demonstrate picosecond photo-induced electron transfer rates. Further, at least 2 attachment sites showed negligible activation energy barriers resulting in similar apparent reaction rates at 2.7 and 295K. These are remarkable results considering that neither picosecond photo-induced electron transfer rates nor activationless reaction rates were observed in comparable synthetic systems, though they are common in natural photosynthesis. However, any attempts in understanding how and why our experimental system rep licates Nature will require detailed structural information in order to interpret the observed kinetic data and to guide our future developments. Obtaining high quality crystals in order to solve structures of labeled PpcA mutants so far was elusive. The molecular dynamics simulations combined with in silico mutation followed by validating computational data with experimental X-ray scattering work and HSQC NMR provide us with a valuable tool to visualize structural changes, generate hypotheses about the mechanisms and factors controlling charge transfer and to develop experimental testing approaches. In the past we have developed CHARMM force field parameters for several photosensitizers and obtained promising preliminary results for some of PpcA mutants in their oxidized form linked to Ru(bpy)3 which closely matched X-ray scattering data. In FY2017 our main focus will be on simulations of the most promising PpcA mutants with several new classes of photosensitizers with a particular focus on compounds using earth-abundant elements. Based on our previous experience, we expect that triplicate 300-500 ns all-atom MD simulations of selected PpcA biohybrids with explicit solvent will provide a sufficient sampling of protein conformational space and help us to better rationalize the collected kinetic data on charge transfer rates and SAXS/WAXS scattering profiles as well as the observed perturbations in the NMR data. At the initial stages of the project we will focus on the systems with all three PpcA hemes either oxidized or reduced. This is particularly interesting as it resu lts in a significant change of the total protein change from +4 to +1. All MD simulations will be performed with NAMD 2.8 and CHARMM force field. We will use standard for protein MD conditions: nPT, PME electrostatics, explicit TIP3 water boxes sufficiently large to keep interaction energy negligible between protein mirror images. Later we repeat some simulation with polarizable forcefields and compare results. The analysis of MD trajectories, computational docking and calculation of X-ray scattering profiles will be carried out on our lab computers. The second major goal is to use several rigid and flexible ligand docking approaches in order to predict and optimize binding sites for a new generation of photosensitizers and photosensitizer-catalyst dyads. We will continue to use an MPI version of DOCK6. We previously successful used this code on Fusion and it already resulted in one peer-reviewed publication. Industry partnership: Project URL: http://blogs.anl.gov/solar-energy/ Current FY Hours Used: undetermined amount New FY Requested allocation: 1000000 Q1: 250000 Q2: 250000 Q3: 250000 Q4: 250000 Justification: NAMD is a highly scalable molecular dynamics simulations code. Our past benchmarks on Fusion with PpcA in a water box (~13,000 atoms) showed more than 99% speed-up efficiency with ~1,600 atoms/CPU core and ~80% efficiency with ~400 atoms/core and yielded 5.1 and 15.7 ns/day on 8 and 32 cores, respectively. DOCK 6 typically had more than 95% scaling efficiency on 32-128 cores used in our previous work and we expect to get similar scaling figures with new simulations Storage requirements: 1TB Thank You, The LCRC Accounts System